The endogenous opioid pentapeptides [Met5]-enkephalin (H-Tyr-Gly-Gly-Phe- Met-OH) and [Leu5]-enkephalin (H-Tyr-Gly-Gly-Phe-Leu-OH) are known to interact with several classes of opioid receptors, as are beta-endorphin and dynorphin A. Determination of the function of these peptides has been hampered by their general lack of specificity for single receptor types. The past several years, however, have seen the preparation of more selective analogs of these peptides which are relatively specific for the mu (mu), delta (delta) and kappa (kappa) opioid receptors. The high cost and variable quality of these peptides make it important that significant quantities of highly purified materials be made available for research and potential clinical trials. This project will develop significantly more straightforward methods than currently available for the large scale synthesis of peptides. The proposed work will use multiple one gram lots of the solid phase resin compartmentalized in flexible polypropylene packets for the large scale synthesis of the delta receptor specific peptide Tyr-D-Pen-Gly-Phe-D-Pen (DPDPE). Due to the high cost of the amino acid D-penicillamine (pen) and the disulfide bridge in the peptide, this synthesis will be an exacting test of the methods to be used during the proposed Phase I portion of this research.